CYP epoxygenase derived EETs: from cardiovascular protection to human cancer therapy.

Abstract

Arachidonic acids are converted to eicosanoid mediators by the distinct enzyme systems: cyclooxygenase, lipoxygenase and cytochrome P450 (CYP) monooxygenase pathways (ω/ω⁻¹-hydroxylases and epoxygenases). CYP2J2, CYP2C8 and CYP2C9 are the predominant epoxygenase isoforms abundantly expressed in the endothelium, myocardium, and kidney in human. The primary epoxidation products by epoxygenases are four regioisomers of cis-epoxyeicosatrienoic acids (EETs): 5,6-, 8,9-, 11,12-, and 14,15-EETs. Numerous studies demonstrated that the cardiovascular protective effects of CYP epoxygenases and EETs range from vasodilation, anti-hypertension, pro-angiogenesis, anti-atherosclerosis, and anti-inflammation to anti-injury caused by ischemia-reperfusion. The roles of arachidonic acids and its metabolites in cancer biology have recently attracted great attentions. However, CYP epoxygenase derived EETs and cancer has received little attention. It was demonstrated that CYP epoxygenases and EETs are significantly upregulated in human tumors and promote tumor progression and metastasis. Additionally, specific inhibitors of CYP2J2, derived from terfenadine, exhibit strong anti-tumor activity in vitro and in vivo. It is implicated that CYP2J2 may be a therapeutic target for treating human cancers.

• Authors: Chen Chen, Dao Wen Wang
• Journal: Current topics in medicinal chemistry (Curr Top Med Chem) Vol. 13 Issue 12 Pg. 1454-69 ( 2013) ISSN: 1873-4294 [Electronic] United Arab Emirates
• PMID: 23688135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• CYP2J2 protein, human
• Cytochrome P-450 Enzyme Inhibitors
• Enzyme Inhibitors
• Terfenadine
• Cytochrome P-450 Enzyme System
• Cytochrome P-450 CYP2J2
• 8,11,14-Eicosatrienoic Acid

Topics

• 8,11,14-Eicosatrienoic Acid (chemistry, metabolism)
• Cardiovascular Diseases (prevention & control)
• Cytochrome P-450 CYP2J2
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Enzyme System (metabolism)
• Enzyme Inhibitors (chemistry, pharmacology)
• Humans
• Neoplasms (drug therapy, metabolism)
• Structure-Activity Relationship
• Terfenadine (chemistry, pharmacology)